PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Leukoencephalopathy, Progressive Multifocal”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2005

The atypical antipsychotic agents ziprasidone [correction of zisprasidone], risperdone and olanzapine as treatment for and prophylaxis against progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is an unremitting, advancing disease of central nervous system white matter. PML is caused by infection of the JC polyoma virus, most always in patients with immunosupression due to, for example, cancer, anti-rejection transplant medications or HIV. There is no specific treatment or cure for PML, and untreated it has a median life expectancy is less than four months. Highly active antiretroviral treatment (HAART) has greatly reduced the incidence and prevalence of PML in HIV+ patients likely, however, even in the best case scenario of an HIV+ patient with PML and taking HAART, a significant mortality remains. Novel treatments for PML are needed. Recently Atwood and colleagues have found that the cellular receptor for JC virus is the serotonin 5HT2A receptor. In vitro they used the older antipsychotic medications chlorpromazine and clozapine to block the serotonin 5HT2A receptor and block JC virus cell entry. Unfortunately, however, chlorpromazine and clozapine have such significant side effects and toxicities, e.g., extrapyramidal symptoms and the possibility of bone marrow dyscrasias - that they may be problematic to use clinically. Here, we point out that some newer atypical antipsychotics such as zisprasidone, risperidone and olanzapine--medicines with much better side effect and toxicity profiles than the older antipsychotics--in vitro are significantly more potent 5HT2A receptor antagonists than chlorpromazine or clozapine by in some cases more than a factor of 10, and thus may be useful as treatment for or prophylaxis against PML.

Antipsychotic Agents↗
PubMed1994

p53 and proliferating cell nuclear antigen expression in JC virus-infected cells of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system (CNS) caused by infection with JC papova virus (JCV), is characterized by marked atypical changes in the glial cells. The JCV T protein binds cellular p53 (a tumor suppressor gene product), which as a result loses its normal down regulating influence on the cell cycle. We hypothesized that this binding would stabilize p53 and prolong its half life, leading to its immunohistochemical detection. To prove our theory combined JCV DNA:DNA in situ hybridization (ISH) and glial fibrillary acidic protein (GFAP) immunohistochemistry (IHC) as well as p53/GFAP double IHC were performed on routinely processed sections of five brains obtained at autopsy and two cerebral biopsy specimens from seven patients with PML. All specimens showed JCV infected oligodendrocytes and bizarre looking astrocytes that immunostained strongly for p53. In addition, because loss of p53 function results in proliferating cell nuclear antigen (PCNA) overexpression PCNA/GFAP double IHC was carried out, and a positive immunoreaction was obtained in JCV infected cells in the two biopsy specimens. The evidence of p53 immunoreactivity in JCV harboring glial cells seems to indicate a link between the JCV induced stabilization/inactivation of p53 and the striking tumorlike glial changes seen in PML. Proliferating cell nuclear antigen overexpression in these cells further supports this pathogenetic construct.

Adolescent↗
PubMed1999

Association of human herpesvirus 6 with the demyelinative lesions of progressive multifocal leukoencephalopathy.

Progressive Multifocal Leukoencephalopathy (PML) is a primary demyelinating disease of the central nervous system occurring almost exclusively in individuals with impaired cell-mediated immunity. The JC polyoma virus has been accepted as the etiologic agent ofPML. Using a two-step in-situ polymerase chain reaction procedure to amplify and detect genomic DNA of human herpesvirus-6 (HHV6) in formalin-fixed paraffin-embedded archival brain tissues, a high frequency of infected cells was consistently detected in PML white matter both within and surrounding demyelinative lesions and HHV6 genome was found mainly within oligodendrocytes. Lesser amounts of HHV6 genome were detected in most normal, AIDS, and other neurological disease control tissues. Immunocytochemistry for HHV6 antigens showed actively infected nuclei of swollen oligodendrocytic morphology only within the demyelinative lesions of PML but not in adjacent uninvolved tissue. In addition, no HHV6 antigens were detectable in control tissues including brains of individuals with HIV-1 encephalopathy but without PML. Double immunohistochemical staining for JC virus large T antigen and HHV6 antigens demonstrated co-labeling of many swollen intralesional oligodendrocytes in the PML cases. The evidence suggests that HHV6 activation in conjunction with JC virus infection is associated with the demyelinative lesions of PML.

AIDS Dementia Complex↗
PubMed1997

Comprehensive investigation of the presence of JC virus in AIDS patients with and without progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML), a viral-induced demyelinating disease, is becoming relatively common, while many diagnostic and pathogenetic aspects remain to be clarified. A study was therefore undertaken in 64 AIDS patients suffering from various neurological disorders, including PML (12 subjects), with the specific objective of searching for JC virus (JCV) DNA by nested PCR (n-PCR) in cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs), and urine collected from all patients. CSF examination, CD4 and CD8 counts, neurological examinations, and neuroradiological investigations were undertaken. JCV DNA was detected in 92% of CSF specimens in 75% of the PBMCs and urine samples from the PML patients, whereas among the non-PML patients JCV DNA was not detected in any CSF samples, but was found in 10% of PBMCs and in 39% of the urine specimens. BKV and JCV DNA viruria was observed simultaneously in 6% of the AIDS patients without PML. The routine CSF tests including IgG oligoclonal bands, the Link, and Tourtellotte IgG indexes, did not show a typical pattern in PML cases. The data obtained clearly indicate that the detection of JCV DNA in CSF constitutes an efficient marker for PML diagnosis. The simultaneous presence of JCV DNA in the CSF, PBMCs, and urine samples from the PML patients, who did not differ from controls with regard to their immunosuppressive status, suggests that JCV could be carried into the central nervous system (CNS) by infected PBMCs.

AIDS-Related Opportunistic Infections↗
PubMed1995

JC virus DNA in cerebrospinal fluid of human immunodeficiency virus-infected patients: predictive value for progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a lytic infection of oligodendrocytes by the human papovavirus JC. Patients with defects in cell-mediated immunity are at risk for active disease: a usually lethal demyelination of the brain. PML develops in at least 4% of patients with the acquired immunodeficiency syndrome (AIDS). Definitive diagnosis currently requires brain biopsy. Previous attempts to detect JC virus DNA by polymerase chain reaction in cerebrospinal fluid of PML patients, particularly those with human immunodeficiency virus type 1 (HIV-1) infection, have been of low sensitivity. In the present study, cerebrospinal fluid was assayed by polymerase chain reaction from 26 HIV-1-positive patients with PML, 114 HIV-1-positive control subjects, and 16 control subjects who were HIV-1 negative or were without risk factors for HIV disease. Polymerase chain reaction conditions were optimized to detect a single copy of viral DNA in 50 microliters of cerebrospinal fluid. Specificity of the polymerase chain reaction product was confirmed by size on gel electrophoresis and Southern blot hybridization. JC virus DNA was detected in 24 of 26 samples from patients with PML: 8 of 8 with tissue diagnosis and 16 of 18 with strong clinical and magnetic resonance imaging evidence of PML. Among control subjects, 11 of 130 samples were positive for JC virus: 10 of 114 samples from HIV-infected patients and one from an HIV-negative patient with risk factors for PML and an unexplained hemiparesis. Overall sensitivity was 92% (24/26); specificity was, at minimum, 92% (119/130). Treatments for PML are now in clinical trials.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1995

PCR detection of JC virus DNA in brain tissue from patients with and without progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system, which is thought to be a result of the reactivation of JC virus (JCV), a human polyomavirus. The disease occurs in individuals with immunosuppression and in recent years there has been an increase in PML cases due to AIDS. A nested polymerase chain reaction (n-PCR) was employed to detect JCV and BK virus (BKV) DNA in brain tissue collected postmortem from 28 AIDS patients with PML and from 13 patients without PML, but with other diagnoses, including solid tumors, Alzheimer's disease, thromboembolism, myocardial infarction and acute cerebrovascular diseases. All 28 brain specimens from the patients with PML were positive for JCV DNA when tested by n-PCR and three of the latter were also positive for BKV DNA. These results were confirmed by an enzyme restriction analysis and a DNA hybridization assay. Interestingly, in this study, JCV DNA was also found in 6 brain tissue specimens from 4 subjects with diseases unrelated to PML or AIDS. All the brain specimens from the control group were negative for BKV DNA. The results confirm that the n-PCR is a useful tool for PML diagnosis. The presence of JCV DNA in the brain tissue of patients without PML is particularly important since it indicates that JCV could be latent in the brains of immunocompetent individuals. Moreover, detection of simultaneous presence of JCV and BKV in the brain tissue of the patients with PML demonstrates that BKV may also infect the human brain without causing any apparent neurological disease.

AIDS-Related Opportunistic Infections↗
PubMed1998

Amplification of JC virus regulatory DNA sequences from cerebrospinal fluid: diagnostic value for progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease in the central nervous system caused by a ubiquitous human polyomavirus designated as JC virus (JCV). PML affects individuals with decreased immune competence and is now one of the common opportunistic infections in patients with AIDS. JCV DNAs in the brain of PML patients contain various PML-type regulatory regions that were generated from the archetypal regulatory region during persistence. Recently, many studies have suggested that detection of JCV DNA from the cerebrospinal fluid (CSF) may offer a tool for diagnosing PML. However, in all of these studies, coding sequences within the T antigen or capsid protein gene have been targeted for amplification. To amplify the JCV regulatory region, we established a nested PCR that could efficiently amplify the regulatory region from most JCV subtypes prevalent in the world. Using this PCR, we amplified JCV regulatory regions from the CSF samples from 4 patients strongly suspected of PML, whereas amplification was negative from 80 CSF samples from patients without PML. Sequencing of the amplified fragments revealed that they had unique deletions and/or duplications. Furthermore, in 3 PML patients, we analyzed the structures of regulatory regions derived from the brain as well as CSF. In each of these cases, the major regulatory sequence of both origins were identical. This finding indicates that JCV DNA in brain lesions is excreted in the CSF. Since the structures of PML-type JCV regulatory regions are unique to individual patients, the current PCR, if the amplified fragments are sequenced, can eliminate false positives that may arise from contaminations.

Brain↗
PubMed1992

Detection of JC virus DNA in peripheral lymphocytes from patients with and without progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) results from lytic infection of oligodendrocytes by JC virus (JCV). Although JCV has been identified in mononuclear cells in bone marrow and hematogenous dissemination of the virus to the central nervous system has been suspected, JCV has never been clearly demonstrated in the peripheral circulation. Using polymerase chain reaction technology, we examined peripheral lymphocytes of 19 patients with brain biopsy-proven PML for the JCV genome. Two non-PML control groups, consisting of 26 patients seopositive for human immunodeficiency virus type 1 (HIV-1) and 30 immunocompetent patients with Parkinson's disease, were also examined for the presence of the JCV genome in lymphocytes. Cerebrospinal fluid from 10 patients with PML was examined for the presence of the JCV genome as well. The JCV genome was detected in the lymphocytes of 89% (17) of the patients with PML, 38% (10) of the HIV-1-seropositive patients without PML, and none of the patients with Parkinson's disease. Sequencing of the JCV regulatory region from the lymphocytes of three patients revealed the prototype MAD-1 strain of JCV in one patient with PML, a MAD-4 strain in a second patient with PML, and a slightly modified MAD-4 strain in an HIV-1-positive patient without PML. Only 3 of 10 patients with PML who had JCV detected in lymphocytes had the JCV genome in their cerebrospinal fluid. These results demonstrate that the JCV genome can be found in circulating lymphocytes from patients with PML and suggest that lymphocytes are an important vector for hematogenous dissemination of JCV to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed2000

Analysis of the transcriptional control region in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease caused by the human polyomavirus JCV. The hypervariable noncoding transcriptional control region (TCR) largely regulates replication of JCV in glial cells. Two distinct types of the TCR can be distinguished. Type II is derived from the archetype sequence. All type I TCRs, including the prototypical Mad-1 isolate contain a 23 bp deletion at nucleotide position 36. In a prospective study, TCR-DNA could be amplified and sequenced in 16/29 (55%) suspect cases of PML from the cerebrospinal fluid (CSF) and in 14/28 (50%) urine samples. Sequencing of the CSF-TCR identified Mad-1 like sequences in 5/17 (29.5%) instances and a type II TCR in 12/17 (70.5%) of cases. Of 14 urine TCRs, 12 (86%) displayed the archetype sequence, while two showed complex rearrangements. In all type II TCR sequences, the tst-1/oct-6 binding sites present in regions C and E of Mad-1 were missing. In 11/12 type II TCR sequences the pentanucleotide repeat in region A showed a G to T substitution of one nucleotide at position 36 relative to the Mad-1 TCR. All type II TCRs contained an Sp1 binding site at the beginning of region B. Of the 12 TCR type II sequences, 10 (83%) were of the 'D-retaining' pattern. In eight of these (80%) additional juxtapositioned nuclear factor 1, glial factor 1 and/or AP-1 binding motifs were created by duplications and/or insertions in region D. These findings indicate that type II TCRs are frequently present in PML and suggest to use TCR type II constructs for in vitro and in vivo studies of the evaluation of the functional role of DNA binding motifs.

Base Sequence↗
PubMed2003

Identical rearranged forms of JC polyomavirus transcriptional control region in plasma and cerebrospinal fluid of acquired immunodeficiency syndrome patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by the human polyomavirus JC (JCV). JCV has a hypervariable noncoding transcriptional control region (TCR) that spans the origin of replication of the JCV genome through to the first ATG start codon for late gene transcription. The archetype form of TCR is frequently found in the urine and kidneys of healthy and immunocompromised subjects. However the rearranged forms, whose prototype is Mad-1, possibly generated by deletion and duplication of segments of the archetype sequence, are found in the brain and cerebrospinal fluid (CSF) of PML patients. In this study the authors compared JCV TCR detected in paired CSF, plasma, and urine samples of 11 acquired immunodeficiency syndrome (AIDS) patients affected by PML to try to determine where the rearranged JCV TCRs are selected. In one patient, it was also possible to amplify and sequence the TCR in the brain and lymphocytes. Moreover, in 5/11 patients, the CSF, plasma, and urine samples corresponding to 2 months after PML development were available; and in another patient, it was possible to sequence the TCR in plasma and lymphocytes sampled 8 months before the onset of PML. The presence of the same TCR sequences in all the CSF and plasma samples taken from individual patients could strengthen the hypothesis that the blood is a compartment where JCV may replicate and undergo rearrangement of the TCR. This further supports the hypothesis that JCV reaches the brain by a hematogenous route and indicates that the JCV TCR sequences detected in plasma could be used as an early marker of JCV pathogenicity before the clinical appearance of PML in immunocompromised patients.

AIDS-Related Opportunistic Infections↗
PubMed2002

Semiquantitative detection of JCV-DNA in peripheral blood leukocytes from HIV-1-infected patients with or without progressive multifocal leukoencephalopathy.

Progressive Multifocal Leukoencephalopathy (PML) is a severe and fatal demyelinating disease that occurs especially in HIV-infected patients. It has been suggested that JC virus (JCV) migrates in peripheral blood leukocytes from the kidney to the central nervous system where it initiates demyelination. To investigate the physiopathological role of the peripheral blood virus in the development of PML, the prevalence of JCV infection and the levels of JCV DNA load were evaluated in peripheral blood leukocytes or mononuclear cells of 10 AIDS patients at the time of onset of PML symptoms, and in 150 non-PML HIV-1-infected patients using a semiquantitative PCR and ELISA-hybridization assay. In PML-AIDS patients, 60% (6/10) were positive for JCV-DNA detection in peripheral blood cells compared with 26% (13/50) and 18% (18/100) positive for non-PML HIV-infected control patients with CD4+ T lymphocyte counts below and above 200.10(6) /l, respectively (60 vs. 26%, P = 0.06; 60 vs. 18%; P = 0.007). The prevalence of JCV infection in the peripheral blood cells taken from controls appeared to be independent of the CDC stage of infection and CD4+ T lymphocyte counts. The predictive positive value of a positive JCV DNA PCR in peripheral blood cells for the diagnosis of PML in an HIV-infected patient was 16% whereas the predictive negative value was 96%. The levels of circulating JCV DNA load, ranging from 1.69 to 2.53 log of copies per 10(6) cells, did not differ between patients at time of PML symptoms onset and controls, and appeared to be independent of the clinical and the biological status in control patients. The findings do not indicate any significant JCV genomic replication activity in peripheral blood cells at the onset of PML disease, and suggest that JCV replication markers in the systemic compartment would not be valuable for predicting the development of PML in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed2004

New JC virus infection patterns by in situ polymerase chain reaction in brains of acquired immunodeficiency syndrome patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML), caused by the human polyomavirus JC (JCV), is an opportunistic infection of the central nervous system (CNS), the histopathological diagnosis of which can be made by routine staining. Very low copy numbers of JCV nucleic acid can be detected in paraffin sections by the specific and highly sensitive in situ polymerase chain reaction (in situ PCR). The authors evaluated JCV infection in 12 acquired immunodeficiency syndrome (AIDS) patients with PML by comparison of hematoxylin and eosin (H&E) staining, in situ hybridization (ISH), and in situ PCR. Phenotype of infected cells was determined by immunohistochemistry with antibodies against glial fibrillary acidic protein (GFAP) or cluster of differentiation 68 (CD68), focusing on cells containing low JC viral copy numbers, and on cell types that are normally not associated with papovavirus infection. The number of detectable JCV-positive oligodendrocytes increased markedly upon PCR amplification and hitherto unknown oligodendrocytic staining patterns were discernible: JCV DNA was detectable in both nucleus and cytoplasm, in cytoplasm only, and as ghost-cell silhouettes appearing as a membranous "rim" of staining product in some cells. The authors suggest that the staining patterns correspond to different stages of the viral replication cycle. Some human immunodeficiency virus (HIV)-type giant cells (HIV-GCs) were shown to contain JCV DNA, thus probably revealing a double infection. Macrophages and HIV-GCs showed staining in the cytoplasm and the nuclei, indicating that they not only may phagocytize JCV particles but may also be actively infected. CD68-positive GCs were occasionally noted to contain a complete JCV DNA-positive nucleus in their center, and were accordingly called JCV-type giant cells (JCV-GCs). Rarely, JCV DNA signals were noted in vascular endothelium. No JCV infection was detectable in lymphocytes, neurons, or in brain tissue of JCV-negative age-matched controls. The authors report new findings concerning inter- and intracellular JCV infection patterns in PML, possibly shedding new light on JCV susceptibility of different cell types in the brain of AIDS patients with PML.

Acquired Immunodeficiency Syndrome↗
PubMed2001

JC virus-specific cytotoxic T lymphocytes in individuals with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the polyomavirus JC (JCV) within a setting of immunosuppression. The nature of the immune response that contains replication of this virus is unknown. We have explored JCV-specific cellular immune responses in patients with PML and control subjects. JCV antigen-stimulated peripheral blood mononuclear cells (PBMC) of four human immunodeficiency virus (HIV)-infected patients who were survivors of PML and one HIV-uninfected patient recently diagnosed with PML lysed autologous B-lymphoblastoid cell lines expressing either the JCV T regulatory protein or the VP1 major capsid protein. This lysis was mediated by CD8(+) T lymphocytes and was major histocompatibility complex class I restricted. These cells were therefore cytotoxic T lymphocytes (CTL). JCV-specific CTL could not be detected in PBMC of three HIV-infected PML patients who had progressive neurologic disease and an eventual fatal outcome. These data suggest that the JCV-specific cellular immune response may play a crucial role in the containment of PML. This finding may also prove useful as a favorable prognostic marker in the clinical management of these patients.

Antigens, Polyomavirus Transforming↗
PubMed1992

Expression of major histocompatibility complex antigens in the brains of patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is caused by JC virus (JCV) infection of the central nervous system (CNS) in immunosuppressed patients. The immunopathogenesis of this chronic encephalitis is unknown. Because major histocompatibility (MHC) class I and class II antigens are important in modulating the immune response and viral clearance, we examined the tissue expression of MHC molecules in relation to CNS damage and presence of virus. By immunocytochemical staining, both MHC class I and class II antigens were expressed at high levels within PML lesions. Beta-2 microglobulin (beta-2m) was present on endothelial cells and JCV-infected oligodendroglia within the lesions. Also, many astrocytes with bizarre morphology expressed MHC class I antigens. In histologically normal regions of PML brains expression of beta-2m was noted only on endothelial cells. Expression of MHC class II also was focused within demyelinating lesions and was restricted to macrophages/microglia and occasional endothelial cells. When compared to other viral encephalitides (e.g. human immunodeficiency virus) these findings suggest that intra-CNS immune response to JCV is appropriate for antigenic presentation; however, the absence of responsive systemic T-cells may lead to chronic viral infection with progressive neuropathology.

Acquired Immunodeficiency Syndrome↗
PubMed2004

A prospective study demonstrates an association between JC virus-specific cytotoxic T lymphocytes and the early control of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the CNS of immunosuppressed individuals caused by the polyomavirus JC (JCV). In previous studies, we showed that JCV-specific cytotoxic T lymphocytes (JCV-specific CTL) were associated with a favourable outcome in patients with PML. However, these CTL had been assessed in PML survivors more than 1 year after the onset of disease and we could not determine whether this immune response was only a surrogate marker for a general recovery of the patient's immune system or a causal factor in the patient's neurological improvement. In this study, we assessed the relationship between JCV-specific CTL detected early in the course of PML and the subsequent course of disease activity. We enrolled 26 patients with possible or proven PML, including 21 HIV+ patients, less than 10 months after the onset of their neurological symptoms (3.7 +/- 2.5 months, median +/- interquartile range). JCV-specific CTL were detected by either 51Cr release or tetramer staining assay. Patients were then followed prospectively and the clinical course of PML was determined. At the time of their first immune evaluation, we found that 15 patients had detectable JCV-specific CTL. HIV+ patients with JCV-specific CTL had a higher CD4+ T-cell count (215 +/- 103/microl) and a lower HIV viral load (144 +/- 431 copies/ml) than those without JCV-specific CTL (32 +/- 59/microl, P = 0.004 and 43 100 +/- 54 778 copies/ml, P = 0.01). Thirteen of these 15 patients with JCV-specific CTL developed clinically quiescent PML, while only two out of 11 without detectable CTL controlled their neurological disease. Therefore, the early detection of JCV-specific CTL had an 87% predictive value for subsequent control of PML, while the absence of such CTL had an 82% predictive value for subsequent active PML (P = 0.0009). Fifteen patients were evaluated less than 4 months after the onset of PML (1.9 +/- 1.3 months). Of nine patients with JCV-specific CTL, seven (78%) demonstrated subsequent control of disease, whereas six out of six (100%) without JCV-specific CTL developed progressive PML (P = 0.007). Two to ten CTL assays were performed on PBMC of 11 patients. Of these patients, one had an increase in JCV-specific CTL preceding a significant clinical improvement. In another patient with otherwise stable immune parameters, a decline in JCV-specific CTL preceded an exacerbation of PML. We conclude that JCV-specific CTL can be detected early in PML and can predict control of this disease. Fluctuations of JCV-specific CTL in the blood are associated with variation in disease manifestations. These results indicate that JCV-specific CTL are associated with the control of PML.

Adult↗
PubMed1995

[Progressive multifocal leukoencephalopathy].

Progressive multifocal leucoencephalopathy (PML) is a rarely occurring demyelinating disease of the central nervous system caused by a neurotropic papovavirus named JC virus (JCV). The most frequently affected areas are the cerebral hemispheres, especially the parieto-occipital region, followed by the cerebellum and brain stem. The disease occurs predominantly in individuals with an immunocompromised state and impaired cellular mediated immunity (CMI) due to other underlying illness. More extensive use of irradiation and immunosuppressive therapy in relation to increased transplantational activities as well as treatment of autoimmune diseases and malignancies, in addition to the appearance of the acquired immunodeficiency syndrome (AIDS) as a consequence of infection with the human immunodeficiency virus (HIV), has caused a considerable increase in the occurrence of PML. The course of the disease is still most often rapidly progressive and fatal, but several cases with prolonged survival and even remission have been reported, and various antiviral treatments have been tried. The only drug that until now has shown favourable results is cytosine arabinoside. In HIV-infected PML-patients immunomodulation with AZT/zidovudine may alleviate the course and improve the prognosis in some patients. Suspicion of PML should lead to an extensive immunological investigation before considering of brain biopsy, which is still the only specific test. On the basis of the increased frequency of PML in relation to HIV-infection, it is likely that our knowledge of the pathogenetic aspects will increase, which, hopefully, may lead to an effective therapeutic strategy. A review of this disease, based upon studies of the literature, is presented.

Diagnosis, Differential↗
PubMed1996

Ophthalmologic manifestations of acquired immune deficiency syndrome-associated progressive multifocal leukoencephalopathy.

PURPOSE: Progressive multifocal leukoencephalopathy (PML) is increasingly described as a late complication of the acquired immune deficiency syndrome (AIDS). The purpose of this study is to evaluate retrospectively the ophthalmologic, clinical, and investigational aspects of AIDS-associated PML. METHODS: The authors evaluated ten patients in whom ophthalmologic manifestations developed in the course of AIDS-associated PML. Findings at clinical examination and their progression over time, neuroimaging correlates, the results of pathologic investigation, and visual outcomes were reviewed. RESULTS: Progressive multifocal leukoencephalopathy was the AIDS-defining illness in six of ten patients. Homonymous visual field defects were the presenting symptom in three patients and detected in six patients overall. Occipital blindness developed in one patient. Cerebellar signs and brain stem nuclear and supranuclear palsies also were common. Confluent white matter lesions with increased intensity on T2-weighted magnetic resonance imaging were supratentorial in seven patients and infratentorial in three patients. With incomplete data, the median survival time was 3 months from PML onset. Histopathologic confirmation of PML diagnosis was available for nine of the ten patients. CONCLUSIONS: The development of progressive retrochiasmal visual field defects, supranuclear and nuclear cranial nerve palsies, or nystagmus ataxia in the relatively young patient should alert the ophthalmologist to the possibility of PML, particularly in the presence of long-tract central nervous system signs or dementia. Progressive multifocal leukoencephalopathy will often be human immunodeficiency virus associated. Human immunodeficiency virus encephalopathy, cerebral toxoplasmosis, lymphoma, and infarction need to be discriminated. Effective therapy is required urgently for this devastating disease.

AIDS Dementia Complex↗